Method of encapsulating hydrophobic organic molecules in polyurea capsules

ABSTRACT

It is known to encapsulate various materials in polyurea microcapsules, but obtaining satisfactory microcapsules incorporating alcoholic materials has proven difficult. A process has now been found where polyurea microcapsules are formed by interfacial polymerization between an aqueous phase and a water-immiscible phase, and properties, particularly the solubility parameters, of the water immiscible phase are closely matched to corresponding properties of the polyurea. Microcapsules prepared by this process have improved stability, mechanical strength and controlled release properties.

FIELD OF THE INVENTION

The present invention relates to microcapsules, and to a process formaking them.

BACKGROUND OF THE INVENTION

Microcapsules containing an encapsulated active ingredient are known formany purposes. In the area of crop protection, insect pheromones thatare slowly released from microcapsules are proving to be a biorationalalternative to conventional hard pesticides. In particular, attractantpheromones can be used effectively in controlling insect populations bydisrupting the mating process. Here, small amounts of species-specificpheromone are dispersed over the area of interest during the matingseason, raising the background level of pheromone to the point where themale insect cannot identify and follow the plume of attractant pheromonereleased by his female mate. Alternatively, pheromones may be used asadditives in microencapsulated pesticides, in order to help attractspecific insects to the microcapsules.

Polymer microcapsules, in particular, serve as efficient deliveryvehicles, as they: a) are easily prepared by a number of interfacial andprecipitation polymerizations, b) enhance the resistance of thepheromone to oxidation and irradiation during storage and release, c)may in principle be tailored to control the rate of release of thepheromone fill, and (d) permit easy application of pheromones by, forexample, spraying, using conventional spraying equipment.

One known method of forming pheromone-filled microcapsules, interfacialpolymerization, involves dissolving a pheromone and a diisocyanate or apolyisocyanate in xylene and dispersing this solution into an aqueoussolution containing a diamine or a polyamine. A polyurea membrane formsrapidly at the interface between the continuous aqueous phase and thedispersed xylene droplets, resulting in formation of microcapsulescontaining the pheromone and xylene; see for example PCT internationalapplication WO 98/45036 [Sengupta et al., published Oct. 15, 1998].

Although this method is useful and yields valuable products, it doeshave some limitations. Isocyanates are highly reactive compounds, and itis at times difficult to encapsulate compounds that react with theisocyanate. For example, it is difficult to encapsulate compoundscontaining hydroxyl groups such as alcohols. Some efforts have succeededin encapsulating alcohols, as seen, for example, in WO 98/45036. Theformed microcapsules, however, lack the stability and mechanicalstrength desirable for commercial use. This may be due to the chemicalreaction between the alcoholic pheromone and the isocyanate, whichreaction competes with wall formation and leads to weaker walls. It mayalso be due to the interfacial activity of the alcoholic pheromone, orthe urethane it forms by reaction with isocyanate, interfering with thecolloidal stability of the microcapsules.

Accordingly, there still remains a need for a process that encapsulatespheromones, particularly alcohol pheromones, to yield microcapsules thathave good storage stability, mechanical strength and controlled releasecharacteristics to permit their successful use in agriculture andhorticulture.

SUMMARY OF THE INVENTION

According to one aspect of the invention there is provided a process forencapsulation of a hydrophobic organic molecule in a polyureamicrocapsule by interfacial polymerization, the process comprisingcontacting

-   -   a) an aqueous phase comprising an amine-bearing compound        selected from a diamine and a polyamine, and    -   b) a water-immiscible phase comprising a water-immiscible        solvent, an isocyanate-bearing compound selected from a        diisocyanate and a polyisocyanate, and a hydrophobic organic        molecule        wherein the water-immiscible solvent has a solubility parameter        that is below the solubility parameter of the polyurea        microcapsule. This may be achieved by choosing an immiscible        phase that has a solubility parameter that is below that of the        polyurea and is preferably within the range of about 3-8        Mpa^(1/2) below the solubility parameter of the polyurea, and        more preferably within the range of 4-6 Mpa^(1/2) below the        solubility parameter of the polyurea. More specifically, and        recognizing that solubility parameters are only very rough        guides to overall polymer-solvent interaction, this may be        achieved by chosing an immiscible phase that may have a        solubility parameter outside of this range, but that by virtue        of its hydrogen bonding interaction or dipolar nature is still        able to slightly swell the polyurea wall.

The most commonly used one-dimensional solubility parameter is theHildebrand solubility parameter. It has been complemented with threedimensional parameters such as the Hansen solubility parameters, thatbreak the overall substance-solvent interaction into three terms: adipolar term, a hydrogen-bonding term, and a dispersive term. Thedispersive term is considered to be of little influence in the presentcontext, dealing with strongly polar and hydrogen-bonded polyurea, andhence emphasis has been placed on the dipolar and hydrogen-bonding termsof the solvents. Examples of these solubility parameters are given inTable 1 below.

Polyurea moities, when formed, display hydrogen bonding. A solvent thatis capable of engaging in hydrogen bonding will cause somesolvent-polyurea hydrogen bonding, thereby interfering to some extentwith polyurea-polyurea hydrogen bonding and causing swelling of thepolyurea.

As well, a permeable polyurea capsule wall may be achieved by choosingan immiscible fill that may have a solubility parameter more thanapproximately 7 Mpa^(1/2) lower than the polyurea, does not engage instrong hydrogen bonding or dipolar interactions with polyurea, but ispolar enough to permit rapid and effective partitioning of the second,aqueous wall forming component, usually a di- or oligoamine, across theinterface and into the immiscible phase. Butyl acetate is an example ofsuch a solvent.

The immiscible phase has to be chosen so as to combine the properties ofhydrogen bonding and polarity, in order to provide an interfacial systemwherein the aqueous amine can rapidly and quantitatively partition intothe immiscible organic phase, throughout the period needed forconversion of the isocyanate.

In other words, in order for the amine to compete effectively with thealcoholic pheromone for reaction with an isocyanate, the amine shouldnot be stopped by a dense, diffusion-limiting polyurea skin. Animmiscible phase chosen to swell the polyurea wall will typically alsohave a fairly high affinity for the amine, and hence facilitatepartitioning of the amine.

Upper limits to the desirable solubility parameters of the encapsulationsolvents are given by the increasing miscibility of the solvent phasewith water, as well as by the decreasing ability of the immiscible phaseto dissolve the hydrophobic fill. For example, as described below,dimethylphthalate (DMP), with a solubility parameter of approximately 22MPa^(1/2), under certain conditions absorbs sufficient water to become apoor solvent for the hydrophobic dodecanol. DMP can be used asimmiscible phase provided a less polar co-solvent such as xylene isadded to reduce the overall solubility parameter of the resultingsolvent mixture.

The invention also extends to a microcapsule comprising awater-immiscible solvent and a hydrophobic organic molecule,encapsulated by a polyurea microcapsule which is swollen by thewater-immiscible solvent. By means of the invention it is possible toprepare microcapsules that encapsulate alcohol in amounts of 5% orgreater, based on the weight of the water-immiscible phase. Examplesbelow show microcapsules made by the process of the invention that havea pheromone loading of 10%, 20% and 30%, based on the weight of thewater-immiscible phase, and that release the pheromone over periods ofsixty days or more. Stability and controlled release over this period oftime is adequate for control of insect populations, as it approximatelyequates to the mating season of insects.

The invention also extends to the formation of polyurea capsulescontaining fills other than alcoholic pheromones, wherein choosing asolvent phase with a solubility parameter as close as feasible to thatof the polyurea capsule wall lead to rapid and quantitative formation ofcapsule walls, that are swollen by the solvent and hence release theirfill readily.

In another aspect, the invention provides the use of a microcapsule, asdescribed above, for the controlled release of a volatile hydrophobicorganic molecule.

DESCRIPTION OF THE FIGURES

Specific embodiments of the invention are further described withreference to the attached Figures, of which:

FIG. 1 shows the weight loss of polyurea (PU) capsules formed fromMondur ML and diethylenetriamine (DETA) with different solvents inabsence of 1-dodecanol.

FIG. 2 shows optical micrographs of the polyurea microcapsules formedfrom Mondur ML and DETA, with 20% 1-dodecanol, and 80% solvent in thecore. The size bar applies to all four images. The solvents were butylacetate (BuAc), propyl acetate (PrAc), butyl benzoate (BuBz) and ethylbenzoate (EtBz).

FIG. 3 shows optical micrographs of polyurea microcapsules formed fromMondur ML and DETA, with 10% 1-dodecanol and 90% solvents in the core,after storage in aqueous suspension for about six months.

FIG. 4 shows typical Environmental Scanning Electron Microscopy (ESEM)and Transmission Electron Microscopy (TEM) images for polyureamicrocapsules formed from Mondur ML and DETA, with 20% 1-dodecanol and80% butyl benzoate in the core.

FIG. 5 graphs the effect of single solvents on the release from polyureacapsules formed from Mondur ML-DETA with 20% 1-dodecanol and 80% solventin the core.

FIG. 6 graphs the effect of co-solvent composition on release frompolyurea capsules formed from Mondur ML-DETA, with 10% 1-dodecanol and90% total cosolvent in the core.

FIG. 7 graphs the effect of co-solvents on the release from polyureacapsules formed from Mondur ML and DETA, with 20% 1-dodecanol and 80%solvent or co-solvents.

FIG. 8 graphs the effect of crosslinking on polyurea capsules formedfrom Mondur ML and Mondur MRS, and DETA and tetraethylenepentamine(TEPA), respectively, with 20% 1-dodecanol and 80% BuBz.

FIG. 9 graphs the effect of 1-dodecanol loading on the release ofpolyurea capsules formed from Mondur ML and TEPA with BuBz as solvent.Mondur ML loading: 2.5%.

FIG. 10 graphs the effect of isocyanate loading on the release frompolyurea capsules formed from Mondur ML and DETA, with 20% 1-dodecanoland 80% BuBz. Mondur ML loading: 2.5%

FIG. 11 shows optical micrographs of polyurea microcapsules formed fromMondur MRS and TEPA, and using 20 mL 1-dodecanol, 40 mL isopropylmyristate and 40 mL methyl isoamyl ketone (MIAK) as the oil phase.

FIG. 12 shows a transmission electron micrograph (TEM) of the polyureacapsules formed from Mondur ML and DETA, using 20% 1-dodecanol and 80%isopropyl myristate for the organic phase.

FIG. 13 shows the results of observations of release rates from polyureacapsules described in FIG. 12, formed with 20% 1-dodecanol and 80%isopropyl myristate and using Mondur ML and DETA.

FIG. 14 illustrates how the in-diffusing amine and oil-bornehydroxy-functional pheromone compete for the available isocyanate ineach forming capsule.

DESCRIPTION OF PREFERRED EMBODIMENTS

The solubility parameter of substances can be used to indicate themiscibility of the substances; the closer the values of the solubilityparameter of two substances the more miscible they generally will be. Inthe case of one of these substances being a crosslinked polymer and theother being a solvent, it is typically found that the closer thesolubility parameters of these two substances, the more the polymer willbe swollen by the solvent. It has been found that by matching thesolubility parameter of the water-immiscible liquid to the solubilityparameter of the crosslinked polyurea that forms the wall of themicrocapsule, within the upper limits described above, there can beobtained microcapsules of enhanced stability and mechanical strength andimproved controlled release characteristics. Polyurea formed fromaromatic isocyanates typically has a solubility parameter ofapproximately 25 Mpa^(1/2). This high value of the solubility parameteris in large part due to the strong internal hydrogen bondingcharacteristic of urea compounds in general.

To prevent formation of a diffusion-limiting polyurea skin at theinterface requires either a strong hydrogen bonding solvent to swell thepolyurea, or a polar solvent with a high affinity towards the amine tofacilitate its in-diffusion. Good hydrogen-bonding properties and highpolarity often go hand-in-hand, and are also highly correlated with thesolubility parameter, as well. Since solubility parameters are known formany solvents, this parameter is used here as one criterion to describethe choice of immiscible phase. It is however not meant to be anexclusive criterion, for the reasons given above.

A suitable water immiscible liquid often has a value of solubilityparameter about 3-8 Mpa^(1/2) below the solubility parameter of thepolyurea, preferably about 4-6 Mpa^(1/2) below the solubility parameterof the polyurea.

The water-immiscible phase is a mixture of substances containing atleast a water-immiscible solvent, a material to be encapsulated such asa hydrophobic pheromone, in particular hydrophobic pheromones containingan alcohol group, and a di- or polyisocyanate, and possibly also one ormore co-solvents. The solubility parameter of interest is the solubilityparameter of this mixture. The closer that this equates to thesolubility parameter of the polyurea, while still remaining immisciblewith water, and able to dissolve the hydrophobic fill, the better theresults obtained, in general.

The solubility parameter of a particular polyurea will depend upon theparticular polyisocyanate and polyamine from which it is formed. Due totheir strong hydrogen bonding ability, and few applications requiringsolvent swelling, the solubililty parameters of polyureas have not beenroutinely measured. They are known to be around 25 Mpa^(1/2) foraromatic polyureas. It is likely that they may be lowered by introducingaliphatic isocyanates, and by incorporating longer spacers between urealinkages. In some preferred embodiments, therefore, a selectedisocyanate is reacted with a selected polyamine to form a polyurea, thevalue of the solubility parameter of the formed polyurea is determined,for example by measuring the physical degree of swelling in a number ofsolvents covering a range of solubility parameters. This value is usedas a guide in determining the solubility parameter, and therefore thecomposition of the water immiscible liquid that is used in theinterfacial polymerization.

The properties of the organic phase are adjusted in terms of polarityand hydrogen bonding ability, to facilitate reaction of the isocyanatewith the amine and to reduce interference from the alcohol when using analcoholic fill. Thus, the composition of the organic phase is adjustedto enhance or maximize the rate and completeness of wall formation, andto achieve control of release rates of both solvent and fill. Inaddition, the release rates of solvent and fill can be controlledthrough the choice of crosslinking agents.

The solvents that have been commonly used as organic phase in the priorart, namely, xylene and toluene, are in general not sufficiently polarfor encapsulation of hydroxyl-functional pheromones in the most commonlyused, aromatic polyureas. It is preferred to use non-reactive liquidsthat have higher polarity and solubility parameters, and mention is madeof aliphatic and aromatic mono- and diesters, especially the C₁-C₁₂alkyl esters of acetic, propionic, succinic, adipic, benzoic andphthalic acid. For esters of aliphatic acids or for esters of aromaticacids, it is preferred that the alkyl moiety has from 1 to 8 carbonatoms. In either case, the alkyl group may be linear or branched. Withdi-acids, the alkyl moieties may be the same or different. Similarly,alkyl esters of longer chain aliphatic acids are suitable, such asisopropyl tetradecanoate, also called isopropyl myristate. It ispossible for the esters to bear additional substituents, for examplealkyl, alkoxy, alkoxyalkyl and alkoxyalkoxy, containing up to 8 carbonatoms.

Suitable solvents also may include esters of ethylene glycol andglycerol, in particular glyceryl triacetate, glyceryl tripropionate,glyceryl tributyrate, and higher triglycerides, as well as acetyltriethyl citrate. Mention is also made of ketones such as methylisobutyl ketone, methyl tert.-butyl ketone, methyl amyl ketone, methylisoamyl ketone and other ketones having up to 12 carbon atoms. Thesesolvents may be used alone or in admixture with each other or inadmixture with other non-polar solvents, for example aromatic solventssuch as toluene and xylene, alicyclic solvents such as cyclohexane, andcommercially available hydrocarbon solvents.

Properties of some organic liquids, and or polyurea are given below:TABLE 1 Hydrogen Hildebrand Polar Bonding Solubility Parameter ParameterBoiling Parameter δ_(p) δ_(h) Point Solvent δ [Mpa^(1/2)] [Mpa^(1/2)][Mpa^(1/2)] [° C.] Xylenes p-: 18.0^(a) o: 1^(a)  o-: 3.1^(a) 137-144m-: 18.2^(b) m: 7.2^(b) m-: 2.4^(b) o-: 18.5^(b) o: 7.5^(b) o-: 0.0^(b)p-: 18.1^(b) p: 7.0^(b) p-: 2.2^(b) butyl benzoate 19.4^(b) 9.4^(b)5.9^(b) 249 butyl acetate 17.4^(a) 3.7^(a) 6.3^(a) 124-126 17.8^(b)7.8^(b) 6.8^(b) Dimethyl 21.9^(a) 10.8^(a)  4.9^(a) 282 phthalate22.5^(b) 12.6^(b)  9.7^(b) Isopropyl 320 myristate Isopropyl 15.3^(a)3.9^(a) 3.7^(a) palmitate Triacetin 22.0^(b) 11.6^(b)  11.2^(b)  258-260Methyl amyl 18.4^(b) 7.6^(b) 7.2^(b) 151.5 ketone Methyl isoamyl17.4^(a) 5.7^(a) 4.1^(a) 142-145 ketone Urea-  25.74^(a)  8.29^(a)12.71^(a) formaldehyde resin (Plastopal H, BASF) 1,1,3,3- 21.7^(a)8.2^(a) 11^(a)   tetramethylurea Polyurea^(c) ˜25    (high)^(a)Polymer Handbook, 4^(th) Ed., Brandrup & Immergut^(b)CRC Handbook of Solubility Parameters and Other Cohesion Parameters,Allan, Barton, CRC Press 1983.^(c)Ryan, A. J.; Stanford, J. L, ; Still, R. H. Polym. Commun. 29(1988),196.

Desirably, the first liquid is a solvent that will swell the formingpolyurea wall. For ease of handling, it should preferably have a boilingpoint in the vicinity of 100° C., or higher. The properties of the firstliquid, which will become encapsulated with the active material that isto be released, will affect the rate of wall formation and the rate ofrelease of that active material. Selection of a first liquid has to bemade with these considerations in mind.

Suitable candidates for use as the first liquid include alkylbenzenessuch as toluene and xylene (provided a polar cosolvent is added toenhance their polarity), halogenated aliphatic hydrocarbons such asdichloromethane, aliphatic nitriles such as propionitrile andbutyronitrile, ethers such as methyl tert.-butyl ether, linear andbranched ketones such as methylisobutylketone and methyl amyl ketone,esters such as ethyl acetate and higher acetates (preferably propylacetate), as well as the analogous propionates, benzoates, adipates andphthalates, and esters of glycerol with acetic, propionic and butyricacid.

Mixtures of solvents can be used. There can also be used co-solvents tochange the solubility parameter of the solvents or solvent mixtures,particularly their polarity and their hydrogen bonding ability. Asco-solvents there are mentioned aliphatic liquids such as kerosene,alicyclic hydrocarbons such as cyclohexane, and hydrophobic esters suchas isopropyl myristate or methyl myristate.

As stated above, xylenes and toluene are insufficiently polar to be usedas the only solvent with a long-chain alcohol that is to beencapsulated. It is possible for a solvent to be too polar to besatisfactorily used, and dimethyl phthalate (DMP) is such a solvent. Inthe case of encapsulation of long-chain alcohols such as dodecanol inpolyurea formed from aromatic isocyanates and short polyamines such asDETA or TEPA for example, it is preferred that the polarity of thewater-immiscible liquid is greater than that of xylenes and toluene, butless than that of DMP. It is possible to use xylenes and toluene assolvent, in admixture with one or more co-solvents such as DMP, oraliphatic esters that enhance its polarity. It is possible to use DMP assolvent, in admixture with one or more co-solvents that reduce itspolarity. Similar considerations apply to the use of polar esters suchas glycerol triacetate, and related polar low molecular weight citricacid esters.

For good release characteristics, it is desirable that the organicsolvent and the hydrophobic active fill shall have the same, or similar,boiling points. It is therefore preferred that the organic solvent andthe hydrophobic fill shall have boiling points that are not more thanabout 50° C. apart, and it is particularly preferred that they shall notbe more than about 20° C. apart. This leads to facilitated transportthrough the capsule wall, with the solvent component helping to swellthe polyurea wall and facilitating release of the active fill.

Alternatively, low boiling solvents such as propyl acetate, butylacetate or methyl isoamyl ketone may be used as well. Here, the solventvaporizes rapidly within the first few hours of release, to be followedby a slower release of the less volatile fill. This situation isacceptable in case of liquid, non-viscous fills, but less desirable inthe case of fills that may crystallize upon loss of solvent from thecore.

The continuous phase is preferably water or an aqueous solution withwater as the major component.

The polyisocyanate may be a diisocyanate, a triisocyanate, or anoligomer. The polyisocyanate may be aromatic or aliphatic and maycontain two, three or more isocyanate groups. Examples of aromaticpolyisocyanates include 2,4- and 2,6-toluene diisocyanate, naphthalenediisocyanate, diphenylmethane diisocyanate (Mondur ML), andtriphenylmethane-p,p′,p″-trityl triisocyanate.

Aliphatic polyisocyanates may optionally be selected from aliphaticpolyisocyanates containing two isocyanate functionalities, threeisocyanate functionalities, or more than three isocyanatefunctionalities, or mixtures of these polyisocyanates. Preferably, thealiphatic polyisocyanate contains 5 to 30 carbons. More preferably, thealiphatic polyisocyanate comprises one or more cycloalkyl moieties.Examples of preferred isocyanates includedicyclohexylmethane-4,4′-diisocyanate; hexamethylene 1,6-diisocyanate;isophorone diisocyanate; trimethyl-hexamethylene diisocyanate; trimer ofhexamethylene 1,6-diisocyanate; trimer of isophorone diisocyanate;1,4-cyclohexane diisocyanate; 1,4-(dimethylisocyanato) cyclohexane;biuret of hexamethylene diisocyanate; urea of hexamethylenediisocyanate; trimethylenediisocyanate; propylene-1,2-diisocyanate; andbutylene-1,2-diisocyanate. Mixtures of polyisocyanates can be used.

Particularly preferred polyisocyanates are polymethylenepolyphenylisocyanates of formula:

wherein n is from 0-4. These compounds are available under thetrade-mark Mondur, with Mondur ML being the compound in which n is 0 andMondur MRS being a mixture of compounds of which n typically is in therange from 0 to 4.

Suitable reactants that will react with isocyanates includewater-soluble primary and secondary polyamines, preferably primarydiamines. These include diamines of formula (I):H₂N(CH₂)_(n)NH₂  (I)wherein n is an integer from 2 to 10, preferably 2 to 6.

Also suitable are mixed primary/secondary amines, and mixedprimary/secondary/tertiary amines. Mixed primary/secondary aminesinclude those of Formula (II):

wherein m is an integer from 1 to 1,000, preferably 1 to 10 and R ishydrogen or a methyl or ethyl group. Mention is made of diethylenetriamine (DETA), tetraethylene pentamine (TEPA), andhexamethylenediamine (HMDA). Suitable primary/secondary/tertiary aminesinclude compounds like those of formula (II), but modified in that oneor more of the hydrogen atoms attached to non-terminal nitrogen atoms ofthe compound of formula (II) is replaced by a lower aminoalkyl groupsuch as an aminoethyl group. The commercial product oftetraethylenepentamine usually contains some isomers branched atnon-terminal nitrogen atoms, so that the molecule contains one or moretertiary amino groups. All these polyamines are readily soluble inwater, which is suitable for use as the aqueous continuous phase. Othersuitable polyamine reactants include polyvinylamine, polyethyleneimine,polypropyleneimine, and polyallylamine.

Primary and secondary amino groups will react with isocyanate moieties.Tertiary amino groups catalyse the reaction of the primary and secondaryamino groups, as well as the conversion of isocyanate groups into aminegroups that can subsequently react further with additional isocyanategroups.

Also suitable are polyetheramines of general formula (III):

where r is an integer from 1 to 20, preferably 2 to 15, more preferably2 to 10, and R is hydrogen, methyl or ethyl. Such compounds, as well astheir analogues based on propyleneoxide repeat units, are availableunder the trademark Jeffamine from Huntsman.

To be useful as a reactant and not merely as a catalyst, the amine mustcontain at least two primary or secondary amino groups. Hence, thecompound must be, at least, a diamine, but it may contain more than twoamino groups; see for example compounds of formula (II). In thisspecification the term “diamine” is used to indicate a compound that hasat least two reactive amino groups, but the term does not necessarilyexclude reactants that contain more than two amino groups.

The pheromone or other material that is to be encapsulated in themicrocapsules is dissolved or dispersed in the solution with theisocyanate. As indicated above, this material must not be so reactivewith the isocyanate that it competes significantly with the reactionthat creates the membrane. Although alcohols will react with isocyanatemoieties to form urethanes, these reactions are relatively slow,compared with the reactions between the isocyanate moiety and the amine,so these reactions do not compete significantly with the desiredmembrane-forming reactions, provided the polyurea formation is fast. Itis an aspect of this invention to teach conditions where thewall-forming reaction of the amine with the polyisocyanate is of thesame order, or faster, than the competing reaction of alcoholic fillswith the polyisocyanates. As stated above, the rate of themembrane-forming reaction depends on the particular liquid that is usedas the dispersed organic phase.

A catalyst can be incorporated with the amine in the aqueous phase tospeed the membrane-forming reactions. Suitable catalysts includetertiary amines. The tertiary amine catalyst, in the amount used, shouldbe freely soluble in the water present in the reaction mixture. Thesimplest tertiary amine is trimethylamine and this compound, and its C₂,C₃ and C₄ homologues can be used. It is of course possible to usetertiary amines containing a mixture of alkyl groups, for instancemethyldiethylamine. The tertiary amine can contain more than onetertiary amine moiety.

The tertiary amine may also contain other functional groups providedthat those other functional groups do not interfere with the requiredreaction, or the functional groups participate beneficially in therequired reaction. As an example of a functional group that does notinterfere there is mentioned an ether group. As examples of groups thatparticipate there are mentioned primary and secondary amino groups, andhydroxyl groups. Examples of suitable tertiary amines include compoundsof the following structures:

Of the tertiary amines, triethylamine (TEA) is preferred.

The amount of the tertiary amine required is not very great. It isconveniently added in the form of a solution containing 0.5 g of TEA per10 mL of water. Usually 0.5% by weight of this solution, based on thetotal weight, suffices, although 0.7% may be required in some cases. Theamount used does not usually exceed 1%, although no disadvantage arisesif more than 1% is used.

Catalysts other than tertiary amines can be used. Metal salts that aresoluble in an organic solvent used as the first liquid can be used.Mention is made of titanium tetraalkoxides available under the trademarkTyzor from DuPont and stannous octanoate, although these should not beused when there is also present in the organic solvent an alcohol to beencapsulated.

The ability to encapsulate alcohols is of particular significance. Thekey component of the pheromone of the codling moth is E,E-8,10-C₁₂alcohol and it has been difficult to encapsulate this pheromone by thepreviously known technique involving isocyanate. The present inventionpermits encapsulation of alcoholic pheromones, and provides long termstorage stability, handling stability and controlled release.

The liquid that serves as the dispersed phase, is a liquid in which theisocyanate can be dispersed or dissolved and in which the pheromone tobe encapsulated can be dispersed or dissolved. The liquid should beimmiscible, or at least only partially miscible, with the aqueous phase.While the limits on what is meant by “partially miscible” are notprecise, in general a substance is considered to be water-immiscible ifits solubility in water is less than about 0.5% by weight. It isconsidered to be water-soluble if its solubility is greater than 98%,i.e., when 1 gram of the substance is put in 100 grams of water, 0.98gram would dissolve. A substance whose solubility falls between theseapproximate limits is considered to be partially water-miscible. Anexample of a partly miscible solvent is glycerol triacetate, which issoluble in 14 parts water.

Surfactants and stabilizers can be used to assist in dispersion oforganic, or oil, phase in the aqueous liquid. Mention is made ofstabilizers such as poly(vinylalcohol), polyvinylpyrrolidones, Methoceland surfactants such as polyoxyethylene(20) sorbitan monooleate,available under the trademark Tween 80. Other suitable surfactants andemulsifiers include polyethyleneglycol alkyl ethers, for exampleC₁₈H₃₅(OCH₂CH₂)_(n)OH, where n has an approximate value of about 20,available under the trade-mark BRIJ 98, or nonylphenyl-oligo-ethyleneglycol, available under the trademark IGEPAL.

Ionic surfactants can be used. Sodium dodecyl sulphate (SDS) ismentioned as an example of an anionic surfactant.

The organic liquid can be dispersed in the aqueous liquid by droppingthe organic liquid into a stirred bath of the aqueous liquid. Theorganic liquid then forms droplets throughout the continuous phase ofthe aqueous liquid. The amine may be present in the aqueous liquidbefore the organic liquid is added. In an alternative, and preferredembodiment, the amine is not present in the aqueous liquid when theorganic liquid is being dispersed, but is added subsequently. In anyevent, the reactants meet and react near the interface between thecontinuous and dispersed phases, that is, near the surface of thedroplets, and react to form the membrane. Specifically, the amine, beingthe more amphiphilic of the two reactants, is usually considered tocross the interface and partition into the organic fill phase, where itreacts with the isocyanate. Hence one consideration in the presentinvention is to provide conditions under which the amine can efficientlypartition into the organic fill phase and hence successfully competewith the alcoholic pheromone in reaction with the isocyanate.

The membrane-forming reaction can be carried out at a temperature above0° C., at room temperature or at elevated temperature. Usually, lowertemperatures such as room temperature, are preferred in the presentinvention, in order to minimize the undesired side reaction betweenisocyanate and alcoholic pheromone. If elevated temperatures are used,the optimum temperature will also depend on the boiling point of each ofthe solvents that make up the dispersed and continuous phases and thatof the material to be encapsulated. No advantage is seen in using atemperature greater than about 70° C. No advantage is anticipated incarrying out the reaction at temperatures below 0° C., in presence offreezing point depressing additives to the aqueous phase.

When microcapsules are formed from a first liquid having a density lessthan that of water, they will usually rise and gather at the top of theliquid present. They can be shipped in this form, or concentrated bydecantation.

As examples of materials to be encapsulated, particular mention is madeof compounds such as insect pheromones. Pheromones containing hydroxylgroups, i.e., alcohols, are of particular interest. These are compoundstypically containing from 8 to 20 carbon atoms and at least one hydroxylgroup, usually a primary hydroxyl group, but sometimes secondary ortertiary. They may be mono- or polyunsaturated and may also contain afurther functional group or groups, for example an epoxy, aldehydic orester group. A compound that is a significant component of severalinsect pheromones, and is a useful model for other pheromones inexperiments, is dodecan-1-ol.

In the notation used herein to describe the structure of the pheromones,the type (E or Z) and position of the double bond or bonds are givenfirst, the number of carbon atoms in the chain is given next and thenature of the end group is given last. To illustrate, the pheromone Z-10C19 aldehyde has the structure:

Pheromones may in fact be mixtures of compounds with one component ofthe mixture predominating, or at least being a significant component.Mentioned as examples of significant or predominant components of insectpheromones, with the target species in brackets, are the following:E/Z-11 C14 aldehyde (Eastern Spruce Budworm), Z-10 C19 aldehyde (YellowHeaded Spruce Sawfly), Z-11 C14 acetate (Oblique Banded Leafroller), Z-8C12 acetate (Oriental Fruit moth) and E,E-8,10 C12 alcohol (Codlingmoth).

An example of a ketone that is a pheromone is E or Z 7-tetradecen-2-one,which is effective with the oriental beetle. An ether that is not apheromone but is of value is 4-allylanisole, which can be used to renderpine trees unattractive to the Southern pine beetle.

As indicated, the invention is particularly useful for encapsulatingalcohols, and mention is made of 1-dodecanol and mono- anddi-unsaturated alcohols, for example E-11-tetradecen-1-ol, Z-11 C₁₄alcohol, Z-8 C₁₂ alcohol and E,E-8,10 dodecadiene-1-ol alcohol. Theinvention is also useful for encapsulating other pheromones such asthose containing ketone, aldehyde or ester groups, as the strong yetpermeable capsule wall formed in presence of suitable polar andhydrogen-bonding solvents will give desirable linear release profiles.

The amount of active fill incorporated in the microcapsules can be up to30% by weight, based on the total weight of the water-immiscible phase.For distributing pheromones for controlled release it is often desirablethat the microcapsule loading shell be as high as possible. In thepresent invention, using alcoholic pheromones, the undesired sidereaction between the pheromone and the isocyanate would increase withincreasing pheromone loading. Successful pheromone loadings of 30% havebeen achieved, as demonstrated below.

In one preferred embodiment, the product of the microencapsulationprocess is a plurality of microcapsules having a size in the range offrom about 1 to about 2000 μm, preferably 10 μm to 500 μm. Particularlypreferred microcapsules have sizes in the range from about 10 μm toabout 60 μm, more preferably about 20 to about 30 μm, and anencapsulated pheromone contained within the capsule membrane. Themicrocapsules can be used in suspension in water to give a suspensionsuitable for aerial spraying. The suspension may contain a suspendingagent, for instance a gum suspending agent such as guar gum, rhamsan gumor xanthan gum.

Incorporation of a light stabilizer, if needed to protect theencapsulated material, is within the scope of the invention. Suitablelight stabilizers include the tertiary phenylene diamine compoundsdisclosed in Canadian Patent No. 1,179,682, the disclosure of which isincorporated by reference. The light stabilizer can be incorporated bydissolving it, with the pheromone, in the organic phase. Antioxidantsand UV absorbers can also be incorporated. Many hindered phenols areknown for this purpose. Mention is made of antioxidants available fromCiba-Geigy under the trademarks Irganox 1010 and 1076. As UV absorbersthere are mentioned Tinuvin 292, 400, 123 and 323 available fromCiba-Geigy.

To assist in determining the distribution of sprayed microcapsules it ispossible to include a coloured dye or pigment in the microcapsules. Thedye should be oil-soluble and can be incorporated, with the pheromone,in the oil phase. It should be used only in a small amount and shouldnot significantly affect the membrane-forming reaction. Alternatively,or additionally, an oil-soluble or oil-dispersible dye can be includedin the aqueous suspension of microcapsules, where it is absorbed by themicrocapsule shell. Suitable oil-soluble or oil-dispersible dyes can beobtained from DayGlo Color Corporation, Cleveland, Ohio, and includeBlaze Orange, Saturn Yellow, Aurora Pink, and the like.

Although the invention has been described largely with reference toencapsulation of pheromones, other molecules that are active in naturecan be encapsulated in a similar manner. As examples there are mentionedlinalool, terpineol, fenchone, and keto-acids and hydroxy-decenoicacids, which encourage activity of worker bees. Encapsulated4-allylanisole can be used to make pine trees unattractive to theSouthern pine beetle. Encapsulated 7,8-epoxy-2-methyloctadecane can beused to combat the nun moth or the gypsy moth.

Other compounds of interest for encapsulation include mercaptans. Someanimals mark territory by means of urine, to discourage other animalsfrom entering that territory. Examples of such animals include preyinganimals such as wolves, lions, dogs, etc. Ingredients in the urine ofsuch animals include mercaptans. By dispersing microcapsules containingthe appropriate mercaptans, it is possible to define a territory anddiscourage particular animals from entering that territory. For example,the urine of a wolf includes a mercaptan, and distribution ofmicrocapsules from which this mercaptan is gradually released to definea territory will discourage deer from entering that territory. Othermaterials that can be encapsulated and used to discourage approach ofanimals include essences of garlic, putrescent eggs and capsaicin.

Other compounds that can be included in the microcapsules of theinvention include perfumes, pharmaceuticals, fragrances, flavouringagents and the like.

It is also possible to encapsulate materials for uses other than innature. Mention is made of dyes, inks, adhesives and reactive materialsthat must be contained until they are to be used, for instance, bycontrolled release from a microcapsule or by rupture of a microcapsule.

Other materials that can be encapsulated are mentioned in PCTinternational application WO 98/45036 mentioned above, the disclosure ofwhich is incorporated herein by reference.

All these applications, and microcapsules containing these materials,are within the scope of the present invention.

The following examples are offered by way of illustration and not by wayof limitation.

EXAMPLES

Formation of Polyurea Capsules by Interfacial Polyaddition

Polyurea (PU) capsules were prepared in a 1 L stirred tank reactor atroom temperature. In a typical experiment, 100 ml organic solventcontaining 2.5 g (10 mmol) Mondur ML was added to 250 ml distilled waterin the reactor. After 5 minutes of mixing at about 400 rpm, 1.03 g (20mmol) diethylene triamine (DETA) dissolved in 50 mL water was added intothe reactor. The aqueous phase contained 0.3 g polyvinyl alcohol (PVA)and/or Tween 80 as a stabilizer or surfactant, respectively. Thereaction was continued for about 4 hours, except where indictedotherwise, and the capsule suspensions were transferred into bottles.

Characterization

An Olympus BH-2 optical microscope (OM) was used to observe theappearance of capsules when they were wet, and during drying. Themorphologies of the capsules were studied with an ElectroScan 2020Environmental Scanning Electron Microscopy (ESEM) and a JEOL 1200EXTransmission Electron Microscope (TEM).

Release Measurement

Release of the core material was measured by gravimetry. Aluminiumweighing dishes treated with sodium carbonate solution were typicallyused as the support for the capsules. Mylar film was used for some ofthe measurements. About 1 mL of capsule-water suspension was spread onthe support in such a way as to form a single layer of capsule ifpossible. These aluminium dishes were placed in a fume hood at ambienttemperature, and the weight of the capsules was measured on a precisebalance until it remained unchanged.

Yield measurement of polyurea-solvent capsules in absence of activefill.

An aliquot of capsule suspension was filtered under vacuum using apre-weighed filter paper, and washed three times with water. The driedcapsules were transferred to a mortar and ground under liquid nitrogen.The broken capsules were then transferred back on to the same filterpaper, washed three times with xylenes, and transferred together withthe filter paper to a dish. These capsule walls were dried at 50° C.,and weighed, and the yield calculated based on theoretical 100%conversion.

Results and Discussion:

1. % Yield of PU walls formed at ambient temperature from differentsolvents containing 2.5% Mondur ML, unless otherwise specified: ReactionTime 4 24 70 hours hours hours PU(xylenes) 2.5%  5% 6.5% PU(xylenes)(for 25% 0.6%  2% 9.5% Mondur ML loading) PU(DMP) 88% PU(BuBz) 11%PU(BuAc) 36%

The interfacial reaction takes place near the interface, morespecifically, on the organic side of the interface. This polyureaformation is a very fast reaction, the two building materials reactingimmediately on contact. Once the primary polyurea wall forms, thesubsequent reaction rate, especially in the case of a poor solvent forpolyurea, largely depends on the continued diffusion of the amine intothe organic phase. More specifically, reaction kinetics may change fromlargely thermodynamic control (amine partitioning into the organicphase), to include diffusion effects (amine diffusing through the formedpolyurea skin). Both partitioning and diffusion through the capsule wallare closely related to the solvent properties and solvent-polymerinteractions. Higher solvent polarity favors amine partitioning, and asolvent with a solubility parameter similar to that of polyurea willswell the forming walls, resulting in better permeability of the polymerwalls for both amine in-diffusion, and potentially, fill release.

The yield results shown above for model capsules not containing1-dodecanol reflect the rate of reaction. When using xylenes as asolvent, all the yields were low even for extended reaction time. Thismay be attributed to both the lower amine partitioning into thisnon-polar solvent, and to the increased resistance to amine diffusionthrough the dense polyurea walls formed. Polyurea is likely to formdense walls in xylenes, due to their poorer solvency/affinity for theforming polymer. The resistance to amine diffusion increasessignificantly as the polymer walls grow. That explains the slowerincrease of the yield with reaction time.

The highest yields were found with DMP as a solvent. Likely the estergroups of DMP favor amine partitioning, and the relatively similarsolubility parameters of DMP and polyurea would cause PU wall swellingand hence further facilitate amine diffusion. It has to be noted thatDMP and xylenes are a suitable solvent for the formation ofmicrocapsules only in the absence of 1-dodecanol. In the presence of1-dodecanol, it is observed that the formed capsules are not stable insuspension but rather aggregate rapidly.

The lower yield observed with BuBz compared to BuAc, is most likely dueto the lower amine partitioning in the less polar BuBz, as well as tothe higher viscosity of the BuBz.

The microcapsules formed from Mondur ML and DETA, at 2.5% Mondur loadingin xylenes, butylacetate, butyl benzoate and dimethylphthalate, after areaction time of 4 hours at room temperature, showed good sphericalshape in the wet state by environmental scanning electron microscopy(ESEM). The microcapsules formed using xylenes (a mixture of o, m and p)as solvent showed well defined polyurea walls, even though the yield waslow and the walls were thin, as revealed by transmission electronmicroscopy (TEM).

The microcapsules formed with dimethyl phthalate (DMP), butyl benzoate(BuBz) and butyl acetate (BuAc) showed thicker, stronger walls, withsome fluffy material found on the inner side of the wall, suggestingthat the ingress of the amine into the organic phase during wallformation had been rapid, at least at some stages of the reaction.

FIG. 1 shows results of observations of release rates from thesemicrocapsules. The microcapsules were formed using Mondur ML at 2.5%loading and DETA, in the absence of 1-dodecanol.

PU(BuAc): very fast release, complete in a few hours. No indication ofresistance for BuAc to diffuse out through the polyurea walls, and BuAcevaporated very fast due to its high volatility.

PU(BuBz): fast release, complete in a few days. Again, no indication ofresistance for BuBz to diffuse out through the polyurea walls. Thehigher boiling point of BuBz needs longer time for its evaporation.

PU(DMP): moderate release, complete in about two months, nearly linear.The low volatility of DMP may contribute to the longer release period ofthis solvent.

PU(xylenes): release rate changes from fast to slow after ˜65% release,and almost stops while release is still incomplete. This slow releasemay be attributed to diffusion-limited release.

FIG. 2 shows optical microscopy images of microcapsules formed fromMondur ML and DETA, with 20% 1-doecanol and 80% of butyl acetate, propylacetate, butyl benzoate, or ethyl benzoate. In each case, sphericalmicrocapsules are observed that are colloidally stable during storage,and mechanically stable during handling. The size bar applies to allfour images in this figure.

FIG. 3 shows optical micrographs of polyurea capsules formed from MondurML and DETA, with 10% 1-dodecanol and 90% total co-solvent mixture,after storage in aqueous suspension for six months. The capsules formedusing propyl acetate/DMP (10%/80%), butyl acetate DMP (10%/80%) andbutyl acetate/DMP (20%/80%) all show spherical shape with no evidencefor aggregation. The size bar applies to all three images in thisfigure.

FIG. 4 shows environmental scanning electron microscopy (ESEM) andtransmission electron microscopy (TEM) images for polyurea capsulesformed from Mondur ML and DETA, with 20% 1-dodecanol and 80% butylbenzoate. These capsules show spherical shape similar to those capsulesformed in absence of 1-dodecanol (not shown). The TEM image showssections of the thin and fairly smooth capsule walls, in agreement withthe low Mondur ML loading of 2.5%.

FIG. 5 shows the effect of using different single solvents, on therelease from polyurea capsules formed from Mondur ML and DETA, with 20%1-dodecanol and 80% solvent in the core. The three solvents used werebutyl benzoate, butyl acetate and propyl acetate. In the case of propylacetate, rapid release is observed during the initial period,corresponding to the low boiling point of propyl acetate, followed by aslow release for about 60 days. In the case of butyl acetate, a similarrelease profile is observed, though the transition from fast to slowrelease is less distinct compared with the case of propyl acetate. Inthe case of butyl benzoate, the transition from rapid to slow release iseven more gradual, in agreement with the higher boiling point of butylbenzoate. In the case of butyl benzoate, the total release is fasterthan in the case of butyl acetate, and much faster than in the case ofpropyl acetate. It is hence suggested that the higher boiling solvent,butyl benzoate, remains in capsules longer than the lower boilingsolvents, and hence can facilitate the release of the 1-dodecanol for alonger period of time.

FIG. 6 shows the effect of co-solvent composition on release frompolyurea microcapsules formed from Mondur ML and DETA, with 10%1-dodecanol and 90% total co-solvent mixtures in the core. Theco-solvent mixtures shown here are based on DMP and Xylenes, withco-solvents chosen to reduce or increase the total solvent polarity,respectively:

-   -   (i) butyl acetate 50%, xylenes 40%;    -   (ii) xylenes 30%, dimethyl phthalate 60%;    -   (iii) propyl acetate 80%, dimethyl phthalate 10%;    -   (iv) propyl acetate 40%, dimethyl phthalate 50%;    -   (v) propyl acetate 10%, dimethyl phthalate 80%.

As FIG. 6 shows, for the three DMP-PrAc co-solvent systems, nearlylinear release profiles were observed. The length of the release periodvaries from about 30 to 100 days as the PrAc fraction changes from 80 to10%. DMP-BuAc co-solvent systems have similar results.

When xylenes were used as a co-solvent, the weight of the residualsamples levelled off at a slightly higher level, suggesting incompleterelease. This is attributed to the poorer match of the properties offill and polyurea even though the other co-solvent (DMP or BuAc) hasalready improved this property match.

FIG. 7 shows graphically results of the effect of using differentwater-immiscible phases on release from microcapsules formed from MondurML/DETA, with 20% 1-dodecanol and 80% total co-solvent. The othercomponents of the water-immiscible liquid were butyl benzoate (80%),butyl benzoate (60%) plus propyl acetate (20%) and propyl acetate (80%)respectively. The results demonstrate again that one can effectivelyadjust the release period by simply changing the co-solvent compositionin the organic phase solvents. The addition of propyl acetate to thebutyl benzoate slows down the fill release due to the poorer solventproperties for the polyurea, i.e., the greater difference between propylacetate and polyurea in solubility parameter, as compared with thedifference between butyl benzoate and polyurea.

FIG. 8 shows graphically results of comparative tests using differentisocyanates, which lead to different polyurea wall characteristics.There was used a water-immiscible fill mixture composed of butylbenzoate as solvent (80%) and 1-dodecanol (20%) as pheromone model, theisocyanate loading being 2.5%. Mondur ML has two isocyanate moieties permolecule, whereas Mondur MRS is a mixture of difunctional and severalhigher functional isocyanates, with on average between of 2.3-2.6isocyanate moieties per molecule, so opportunity for crosslinking isgreater with Mondur MRS.

The amines used were DETA and TEPA. DETA is considered to act mainly asa di-functional amine, with only limited crosslinking through thesecondary amine in the centre of the molecule. TEPA is considered togive comparatively more crosslinking through the secondary andadditional primary amines in the centre of the molecule.

Results of release of fill over time, are shown in FIG. 8 and show thatrelease period is increased when the degree of crosslinking in thepolyurea wall is greater. The capsules formed from Mondur ML/DETArelease completely by about 100 days. Similar effects of crosslinking onrelease were observed when DMP-acetate (butyl and propyl) co-solventsystems were used.

In contrast to the experiments whose results are shown in FIG. 8, whenxylene or DMP was used as solvent in an attempt to encapsulate1-dodecanol at 10% loading, no stable microcapsules formed; initiallyformed capsules coagulated shortly after their formation.

FIG. 9 shows results on release of varying the amount of 1-dodecanolencapsulated. Mondur ML at 2.5% loading and TEPA were used. The fillswere mixtures of 1-dodecanol and butyl benzoate. It is noteworthy thatby selection of appropriate water-immiscible phase the inventors wereable to achieve a 30% loading of pheromone, and also that themicrocapsulation yielded stable microcapsules that released thepheromone over a period of more than 30 days. The effect of 1-dodecanolloading is significant. The increase of loading from 10% to 30% led toan increase in the release period from about 10 days to more than 30days. Much of the weightless during the first approximately five to tendays can be attributed to loss of solvent, butyl benzoate, while therelease of the dodecanol dominates the weight loss during the latterstages of release.

FIG. 10 shows results of experiments in which the isocyanate loading wasvaried. Mondur ML was used at 2.5% and 10% loading, with DETA. The fillwas 20% 1-dodecanol and 80% butyl benzoate. It can be seen that higherisocyanate loading slightly extends the release period, but alsosignificantly slows the release of the dodecanol and leads to retentionof large amounts of fill even after 100 days of release.

FIG. 11 shows optical micrographs of polyurea microcapsules formed fromMondur MRS and tetraethylenepentamine (TEPA). The oil phase consisted of20 mL 1-dodecanol, 40 mL isopropyl myristate and 40 mL methyl isoamylketone (MIAK) and 2.5 g Mondur MRS. The aqueous phase consisted of 300mL distilled water containing 0.1% polyvinyl alcohol (PVA) and 0.5 mL(0.54 g) Tween 80 surfactant. The capsules are formed by emulsifying thecombined oil phase in 250 mL of the aqueous phase for 5 minutes at 400rpm, adding TEPA dissolved in the remaining 50 mL aqueous phase, andreducing the stirring speed to 250 rpm one minute after adding the TEPA.The capsules show spherical shape. Mondur MRS is less soluble inisopropyl myristate than the lower molecular weight analog Mondur ML. Asa result, some of the isopropyl myristate has been replaced with themore polar methyl isoamyl ketone in this example. The mixture ofisopropyl myristate, having a fairly low hydrogen bonding solubilityparameter, and MIAK, having a high hydrogen bonding solubilityparameter, is capable of dissolving both Mondur MRS and the pheromone toform a homogeneous organic phase. In addition, this solvent mixture iscapable of swelling the polyurea wall sufficiently to permit bothin-diffusion of the amine during capsule formation, and release of thefill during the release period. An additional advantage of thiscomposition is that both isopropyl myristate and MIAK are approved foragricultural use in the United States.

FIG. 12 shows a transmission electron micrograph (TEM) of the polyureacapsules formed from Mondur ML and DETA, using 20% 1-dodecanol and 80%isopropyl myristate for the organic phase. The TEM shows the thin, densewall formed at the interface between the aqueous and organic phases.Isopropyl myristate is a branched alkyl ester or a long chain aliphaticacid. Its Hansen hydrogen-bonding and polarity parameters are near thelower end of the range acceptable to achieve sufficient swelling ofaromatic polyurea shells.

FIG. 13 shows the results of observations of release rates from polyureacapsules described in FIG. 12, formed with 20% 1-dodecanol and 80%isopropyl myristate and using Mondur ML and DETA. The graph reflects theresults of weight loss measurements. The numerical values along thegraph indicate the amount of 1-dodecanol remaining in the capsules atthe indicated times. These data indicate that release of 1-dodecanol issubstantially complete after 150 days. These data also indicate that incases such as this, where the solvent has a significantly higher boilingpoint compared with the pheromone, release of the pheromone is stilleffective, as sufficient solvent is present to swell the polyurea wallduring the release phase.

FIG. 14 illustrates how the in-diffusing amine and oil-bornehydroxy-functional pheromone compete for the available isocyanate ineach forming capsule. The undesired urethane-forming side-reaction canbe minimized by using core-solvents that by nature of theirhydrogen-bonding ability and polarity can both physically swell theforming polyurea, and facilitate partitioning of the amine into theorganic phase. In addition, it is helpful if the core-solvents haveboiling points close or higher than that of the pheromone, in order tobe able to swell the polyurea wall during the release period. It isfurther helpful to reduce the isocyanate and pheromone loadings in thecore to 2.5% and 20%, respectively.

In addition to the experiments summarized in the figures, polyureacapsules based on Mondur ML and DETA, as well as Mondur MRS and TEPA,can also be formed using polar, less volatile esters such astriglycerides. Specifically, stable polyurea capsules were formed fromMondur ML and DETA, with 20% 1-dodecanol and 80% glycerol tributyrate inthe core. Similar capsules may also be formed using glycerol tributyrateor other triglycerides, in conjunction with other solvents.

As stated above, attempts to encapsulate 1-dodecanol at 10% loading inDMP, alone did not result in formation of stable microcapsules. Inexperiments with solvents of lower polarity than DMP success wasachieved. Thus success was achieved with dibutyl phthalate (DBP) (90%)and 1-dodecanol (10%). Success was also achieved with microcapsules ofMondur ML at 2.5% loading and DETA with fills of propyl acetate (80%)plus 1-dodecanol (20%) and of butyl acetate (80%) plus 1-dodecanol(20%), as well as with fills of ethylbenzoate (80%) and 1-dodecanol(20%) and with butyl benzoate (80%) and 1-dodecanol (20%). Results ofweight loss measurements as an indicator of fill release for some ofthese cases are shown graphically in FIG. 5.

Encapsulation of 1-dodecanol with butyl benzoate as solvent wassuccessful at loadings of 10%, 20% and 30%, using Mondur ML at 2.5%loading and TEPA, and results are shown in FIG. 9. Encapsulationattempts with ethyl benzoate as sole solvent were successful, but thosewith methyl benzoate as sole solvent were unsuccessful and themicrocapsules coagulated during the last stages of reaction. It isbelieved that methyl benzoate is too polar and that admixture with aco-solvent to reduce polarity somewhat would enable it to be usedsuccessfully.

While DMP can not be used as a single solvent in the encapsulation of1-dodecanol, DMP with a small amount of less polar co-solvent works wellfor this purpose. DMP/BuAc and DMP/PrAc, with the co-solvent ratioranging from 1/8 to 8/1 and containing 1 part (10%) 1-dodecanol, weretested. Similarly, DMP/xylenes and BuAc/xylenes at co-solvent ratio upto 5/4 were also tested, again with 1 part (10%) dodecanol. Stablecapsules were observed in each case. However, the capsules preparedusing xylenes as a co-solvent tend to coagulate during storage, and thistendency increases with increasing xylene fraction.

The invention reveals that in the encapsulation of reactive materials,such as 1-dodecanol, the properties of the organic phase in terms ofpolarity, hydrogen bonding ability, and boiling point are very importantfor the formation of stable capsules. Adjusting the properties oforganic phase can be realized by either choosing a suitable solvent orby using a co-solvent.

Butyl benzoate is a good choice as a single solvent to prepare polyureacapsules encapsulating 1-dodecanol. It has good mutual solubility with1-dodecanol, and a similar solubility parameter to that of polyurea. Thecapsules have reasonably good stability, and have a release period ofabout 10 to 30 days when using Mondur ML and DETA to form polyureacapsules with a Mondur loading of 2.5 (w/v) to the organic phase.

Alkyl acetates also have good mutual solubility with 1-dodecanol,however, propyl or butyl acetates evaporated fast at the beginning,leave 1-dodecanol behind for a slow and possibly incomplete release.

DMP-acetate co-solvent systems are a good choice for the encapsulationof 1-dodecanol as regards the stability of the capsules, nearly linearrelease profiles, and the adjustable release period. The release periodvaries from about 30 to 100 days as PrAc fraction changes from 80 to10%.

Isopropyl myristate, and mixtures of isopropyl myristate withmethyl-isoamyl ketone, represent organic phases that fulfill therequirements for sufficient hydrogen-bonding and polarity, and areaccepted for use in agricultural situations. The high boiling point ofisopropyl myristate additionally ensures that it will be present in thecapsules during the release period to swell the capsules and facilitaterelease.

The microcapsule suspension as obtained from the interfacial reactionstill contains residual amounts of stabilizer and/or surfactant. It wasobserved that washing the capsules with water to remove most of thisresidual stabilizer and/or surfactant resulted in increased releaserates, and more complete release over time. This is possibly due to theresidual stabilizers and/or surfactants forming a hydrophilic layer onthe outside of the capsules, that is responsive to humidity and acts asan additional release barrier to the hydrophobic fill.

All publications, patents and patent applications cited in thisspecification are herein incorporated by reference as if each individualpublication, patent or patent application were specifically andindividually indicated to be incorporated by reference. The citation ofany publication is for its disclosure prior to the filing date andshould not be construed as an admission that the present invention isnot entitled to antedate such publication by virtue of prior invention.

Although the foregoing invention has been described in some detail byway of illustration and example for purposes of clarity ofunderstanding, it is readily apparent to those of ordinary skill in theart in light of the teachings of this invention that certain changes andmodifications may be made thereto without departing from the spirit orscope of the appended claims.

It must be noted that as used in this specification and the appendedclaims, the singular forms “a”, “an”, and “the” include plural referenceunless the context clearly dictates otherwise. Unless defined otherwiseall technical and scientific terms used herein have the same meaning ascommonly understood to one of ordinary skill in the art to which thisinvention belongs.

1. A process for encapsulation of a hydrophobic organic molecule in apolyurea microcapsule by interfacial polymerization, the processcomprising contacting c) an aqueous phase comprising an amine-bearingcompound selected from a diamine and a polyamine, and d) awater-immiscible phase comprising a water-immiscible solvent, anisocyanate-bearing compound selected from a diisocyanate and apolyisocyanate, and a hydrophobic organic molecule wherein thewater-immiscible solvent has a solubility parameter that is below thesolubility parameter of the polyurea microcapsule.
 2. The processaccording to claim 1, wherein the solubility parameter of thewater-immiscible solvent is within the range of 3 to 8 Mpa^(1/2) of thesolubility parameter of the polyurea microcapsule.
 3. The processaccording to claim 1 or 2, wherein the polyurea microcapsule is swollenby the water-immiscible solvent.
 4. The process according to any one ofclaims 1 to 3, wherein the water-immiscible solvent has a boiling pointthat is lower than the boiling point of the hydrophobic organicmolecule.
 5. The process according to claim 4 wherein the boiling pointof the water-immiscible solvent is within 60° C. of the boiling point ofthe hydrophobic organic solvent.
 6. The process according to any one ofclaims 1 to 5, wherein the water-immiscible solvent is comprised of twoor more solvent components, and wherein the boiling point of one of thesolvent components is within 20° C. of the boiling point of thehydrophobic organic solvent.
 7. The process according to any one ofclaims 1 to 6, wherein the hydrophobic organic molecule is volatile. 8.The process according to any one of claims 1 to 7, wherein thehydrophobic organic molecule is a pheromone.
 9. The process according toclaim 8, wherein the pheromone comprises a functional group selectedfrom hydroxyl, epoxy, aldehyde and ester.
 10. The process according toany one of claims 1 to 6, wherein the hydrophobic organic moleculecomprises a compound that is selected from the group comprising amercaptan, an essence of garlic, putrescent eggs, capsaicin, a perfume,a pharmaceutical, a fragrance, a flavouring agent, a pigment, a dye, anantioxidant, a light stabilizer, and a UV absorber.
 11. The processaccording to any one of claims 1 to 6, wherein the hydrophobic organicmolecule is selected from an E/Z-11 C₁₄ aldehyde, a Z-10 C₁₉ aldehyde, aZ-11 C₁₄ acetate, a Z-8 C₁₂ acetate, an E,E-8,10 C₁₂ alcohol, E or Z7-tetradecen-2-one, 4-allylanisole, E-11-tetradecen-1-ol, a Z-11 C₁₄alcohol, a Z-8 C₁₂ alcohol, an E,E-8,10 dodecadiene-1-ol alcohol,linalool, terpineol, fenchone, a keto-decenoic acid, a hydroxy-decenoicacid, 4-allylanisole, and 7,8-epoxy-2-methyloctadecane.
 12. The processaccording to any one of claims 1 to 11, wherein the water-immisciblesolvent comprises one or more of a linear or branched C₁-C₁₂ alkyl esteror diester of acetic acid, propionic acid, succinic acid, adipic acid,benzoic acid or phthalic acid.
 13. The process according to any one ofclaims 1 to 11, wherein the water-immiscible solvent comprises a linearor branched C₁-C₁₂ triester of glycerol, or a C₁-C₁₂ diester of ethyleneglycol, propylene glycol or butylene glycol.
 14. The process accordingto any one of claims 1 to 11, wherein the water-immiscible solventcomprises a linear or branched C₁-C₁₂ ester of a linear or branchedaliphatic acid having between 1 and 16 carbons.
 15. A microcapsulecomprising a water-immiscible solvent and a hydrophobic organicmolecule, encapsulated by a polyurea microcapsule which is swollen bythe water-immiscible solvent.
 16. The microcapsule according to claim15, wherein the water-immiscible solvent has a solubility parameter thatis below the solubility parameter of the polyurea microcapsule.
 17. Themicrocapsule according to claim 16, wherein the solubility parameter ofthe water-immiscible solvent is within the range of 3 to 8 Mpa^(1/2) ofthe solubility parameter of the polyurea wall.
 18. The microcapsuleaccording to any one of claims 15 to 17, wherein the hydrophobic organicmolecule is present in an amount greater than 5%, based on the weight ofthe water-immiscible solvent.
 19. The microcapsule according to any oneof claims 15 to 17, wherein the hydrophobic organic molecule is presentin an amount greater than 10%, based on the weight of thewater-immiscible solvent.
 20. The microcapsule according to any one ofclaims 15 to 17, wherein the hydrophobic organic molecule is present inan amount greater than 20%, based on the weight of the water-immisciblesolvent.
 21. The microcapsule according to any one of claims 15 to 17,wherein the hydrophobic organic molecule is present in an amount greaterthan 30%, based on the weight of the water-immiscible solvent.
 22. Themicrocapsules according to any one of claims 15 to 21, wherein thehydrophobic organic molecule is volatile.
 23. The microcapsulesaccording to any one of claims 15 to 22, wherein the hydrophobic organicmolecule is a pheromone.
 24. The microcapsule according to claim 23,wherein the pheromone comprises a functional group selected fromhydroxyl, epoxy, aldehyde and ester.
 25. The microcapsules according toany one of claims 15 to 21, wherein the hydrophobic organic moleculecomprises a compound that is selected from the group comprising amercaptan, an essence of garlic, putrescent eggs, capsaicin, a perfume,a pharmaceutical, a fragrance, a flavouring agent, a pigment, a dye, anantioxidant, a light stabilizer, and a UV absorber.
 26. Themicrocapsules according to any one of claims 15 to 21, wherein thehydrophobic organic molecule is selected from an E/Z-11 C₁₄ aldehyde, aZ-10 C₁₉ aldehyde, a Z-11 C₁₄ acetate, a Z-8 C₁₂ acetate, an E,E-8,10C₁₂ alcohol, E or Z 7-tetradecen-2-one, 4-allylanisole,E-11-tetradecen-1-ol, a Z-11 C₁₄ alcohol, a Z-8 C₁₂ alcohol, an E,E-8,10dodecadiene-1-ol alcohol, linalool, terpineol, fenchone, a keto-decenoicacid, a hydroxy-decenoic acid, 4-allylanisole, and7,8-epoxy-2-methyloctadecane.
 27. The microcapsule according to any oneof claims 15 to 26, wherein the water-immiscible solvent has a boilingpoint which is lower than that of the hydrophobic organic molecule. 28.The microcapsule according to claim 27, wherein the boiling point of thewater-immiscible solvent is within 60° C. of the boiling point of thehydrophobic organic molecule.
 29. The microcapsule according to any oneof claims 15 to 28, wherein the water-immiscible solvent is comprised oftwo or more solvent components, and wherein the boiling point of one ofthe solvent components is within 20° C. of the boiling point of thehydrophobic organic solvent.
 30. The microcapsule according to any oneof claims 15 to 29, wherein the water-immiscible solvent comprises oneor more linear or branched C₁-C₁₂ alkyl esters or diesters of aceticacid, propionic acid, succinic acid, adipic acid, benzoic acid, andphthalic acid.
 31. The microcapsule according to any one of claims 15 to29, wherein the water-immiscible solvent comprises a linear or branchedC₁-C₁₂ triester of glycerol, or a C₁-C₁₂ diester of ethylene glycol,propylene glycol or butylene glycol.
 32. The microcapsule according toany one of claims 15 to 29, wherein the water-immiscible liquidcomprises a linear or branched C₁-C₁₂ ester of a linear or branchedaliphatic acid having between 1 and 16 carbons.
 33. Use of amicrocapsule as claimed in any one of claims 15 to 32, for thecontrolled release of a volatile hydrophobic organic molecule.